Relapsed/Refractory B-Cell MalignanciesPhase 1NCT04943016
CD19 CAR T Cells in Children and Adults With Relapsed or Refractory CD19 Positive B Cell Malignancies
A Phase 1 study testing CD19 Chimeric Antigen Receptor (CAR) T Cells in people with Relapsed/Refractory B-Cell Malignancies, run by National Taiwan University Hospital.
Trial summary
This study seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children and adults with… Read more about this study
- Who is it for?
- Ages 1 year to 65 years
- Conditions the study is for
- Relapsed/Refractory B-Cell Malignancies
- What is being tested?
- CD19 Chimeric Antigen Receptor (CAR) T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2021to 31 Dec 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects must have the ability to understand and the willingness to sign a written informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, between the age of 1 and 65 years
- In good general health as evidenced by medical history and diagnosed relapsed or refractory CD19+ B cell malignancies including acute lymphocytic leukemia (ALL), non-Hodgkin's lymphoma containing Diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or small lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia(BPLL), Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma (MZL).
- Definition of relapse or refractory as below:
- Ineligible hematopoietic transplantation
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- Relapse after transplantation
- Subject with ALL was evaluated by minimal residual disease > 0.1% after treatment with at least two lines of therapy. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated by at least two lines of therapy, including tyrosine kinase inhibitors (TKIs) are eligible.
- Subject with lymphoma treated regimens containing both anti-CD20 antibody and anthracycline-containing chemotherapy regiment. Subjects with transformed follicular lymphoma must have received prior chemotherapy for follicular lymphoma and subsequently have the chemo refractory disease after transformation to diffuse large B-cell lymphoma
- The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
- Performance status: Adult Subjects: ECOG ≤2; Subjects > 10 years of age: Karnofsky≥ 50%; Subjects ≤ 10 years of age: Lansky scale ≥ 50% (See Appendix 1)
- The following laboratory values :
- Total bilirubin ≤ 2x upper limit of normal
- AST (SGOT) ≤ 5x upper limit of normal
- ALT (SGPT) ≤ 5x upper limit of normal
- Serum Creatinine ≤ 2.0 mg/dl
- Subjects must have the following hematologic function parameters (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion):
- i.Absolute lymphocyte count>0.3× 109cells/L ii.Platelets>50 × 109 cells/L
- Prior therapy wash-out: At least 2 weeks or 5 half-lives, whichever is longer, must have elapsed since any prior systemic therapy including cytotoxic chemotherapy, immunomodulatory, immunosuppressive, antiproliferative drugs, antibody, immune checkpoint therapy, pegylatedasparaginase, pegfilgrastimat the time the subject is planned for leukapheresis. Filgrastim, intrathecal methotrexate, systemic steroid, and donor lymphocyte infusion must be stopped 5 days, 7 days, 72 hours, and 4 weeks before leukapheresis, respectively.
- Ability to take oral medication and be willing to adhere to the intervention protocols and medication regimens
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during the follow-up period of the protocol
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
Who cannot join
- Current use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary.
- Pregnancy or lactation
- Known allergic reactions to components used in the intervention protocols or medication regimens in this study
- Active Febrile illness
- Treatment with another investigational drug or other intervention within 30 days or 5 half-lives.
- Autologous transplant within 6weeks of planned CAR-T cell infusion.
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- Patients who are able to obtain market approved CD19 CAR T-cell therapies.
- Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to Enrollment.
- History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
- Active HIV infection.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child-bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study to the follow-up period of the protocol.
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
- Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative viral load prior to enrollment. (viral load positive patients will be excluded.)
- Severe concomitant disease or organic dysfunction that is expected to reduce life expectancy less than 3 months.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Phase I Clinical Trial of CD19 Chimeric Antigen Receptor (CAR) T Cells in Children and Adults With Relapsed or Refractory CD19 Positive B Cell Malignancies
This study seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children and adults with relapsed/refractory B cell malignancies.
Read the detailed description
The overall goal of this study is to validate the safety profile of administration CD19 CAR T cells and describe the toxicities in children and adults with relapsed/ refractory B cell malignancies. The dose is escalated in standard 3 +3 design with a starting dose of
1x106 cell/kilogram and maximum treatment dose of 5 x 106 cell/kilogram. The minimum number of 9 subjects would occur if no dose-limiting toxicities are observed in the 3 dose escalation cohorts. The maximum sample size of 18 subjects would be enrolled in 3 dose escalation cohorts (six in each cohort) for meeting dose-limiting toxicities request. In addition, we hypothesize that we will be able to successfully manufacture CAR T cells to meet the established release criteria at a minimum target dose of 1 X 106 +-30% cells/kilogram in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system.
- Conditions
- Relapsed/Refractory B-Cell Malignancies
- Being tested
- CD19 Chimeric Antigen Receptor (CAR) T Cells
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 Chimeric Antigen Receptor (CAR) T CellsDrug
This study seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children and adults with relapsed/refractory B cell malignancies. The overall goal of this study is to validate the safety profile of administration CD19 CAR T cells and describe the toxicities in children and adults with relapsed/ refractory B cell malignancies. Each patient implements leukapheresis 2 weeks after enrollment and infuse CD19 CAR-T cell around 2 weeks after leukapheresis, and administrated chemotherapy lymphodepletion regimen 1 week before infusion. Furthermore, the treated subject would be following up around 2 years.
| Study group | Role | What they receive |
|---|---|---|
| CD19 Chimeric Antigen Receptor (CAR) T Cells | Experimental | The dose is escalated in standard 3 +3 design with a starting dose of 1x10^6 cell/kilogram and maximum treatment dose of 5 x 10^6 cell/kilogram. The minimum number of 9 subjects would occur if no dose-limiting toxicities are observed in the 3 dose escalation cohorts. The maximum sample size of 18 subjects would be enrolled in 3 dose escalation cohorts (six in each cohort) for meeting dose-limiting toxicities request. In addition, we hypothesize that we will be able to successfully manufacture CAR T cells to meet the established release criteria at a minimum target dose of 1 X 106 +-30% cells/kilogram in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system. Receives: Drug: CD19 Chimeric Antigen Receptor (CAR) T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
80% Proportion of products successfully manufactured meeting the established release criteria with a goal of at least CAR-T cell 1 X 10^6 cells/kilogram.
To examine the feasibility of manufacture of autologous CD19 CAR T-cells at a minimum target dose of 1 X 106 cells/kilogram using the Miltenyi CliniMACS Prodigy® automated system
Measured: 3 years
Incidence and severity of adverse events
To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19
Measured: 3 years
Incidence and severity of Dose Limited Toxicities
Find the recommended phase II dose (RP2D) for recurrent/refractory B cell malignancies
Measured: 3 years
Incidence and severity of Maximum Toxicity Dose
Find the recommended phase II dose (RP2D) for recurrent/refractory B cell malignancies
Measured: 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2021
- Study start1 Jul 2021 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory B-Cell MalignanciesStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04943016
- Sponsor's protocol ID
- 202103150MINC
- Status last verified
- May 2021
- First submitted
- 4 Jun 2021
- Last updated
- 29 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of CD19 Chimeric Antigen Receptor (CAR) T Cells in Children and Adults With Relapsed or Refractory CD19 Positive B Cell Malignancies
- ClinicalTrials.gov ID
- NCT04943016
- Acronym / sponsor ID
- 202103150MINC
- Conditions
- Relapsed/Refractory B-Cell Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Jul 2021 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 29 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children and adults with relapsed/refractory B cell malignancies.
Detailed description
The overall goal of this study is to validate the safety profile of administration CD19 CAR T cells and describe the toxicities in children and adults with relapsed/ refractory B cell malignancies. The dose is escalated in standard 3 +3 design with a starting dose of
1x106 cell/kilogram and maximum treatment dose of 5 x 106 cell/kilogram. The minimum number of 9 subjects would occur if no dose-limiting toxicities are observed in the 3 dose escalation cohorts. The maximum sample size of 18 subjects would be enrolled in 3 dose escalation cohorts (six in each cohort) for meeting dose-limiting toxicities request. In addition, we hypothesize that we will be able to successfully manufacture CAR T cells to meet the established release criteria at a minimum target dose of 1 X 106 +-30% cells/kilogram in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19 Chimeric Antigen Receptor (CAR) T Cells | Experimental | Drug: CD19 Chimeric Antigen Receptor (CAR) T CellsThe dose is escalated in standard 3 +3 design with a starting dose of 1x10^6 cell/kilogram and maximum treatment dose of 5 x 10^6 cell/kilogram. The minimum number of 9 subjects would occur if no dose-limiting toxicities are observed in the 3 dose escalation cohorts. The maximum sample size of 18 subjects would be enrolled in 3 dose escalation cohorts (six in each cohort) for meeting dose-limiting toxicities request. In addition, we hypothesize that we will be able to successfully manufacture CAR T cells to meet the established release criteria at a minimum target dose of 1 X 106 +-30% cells/kilogram in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system. |
Who may qualify
- Ages
- 1 year to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- Subjects must have the ability to understand and the willingness to sign a written informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, between the age of 1 and 65 years
- In good general health as evidenced by medical history and diagnosed relapsed or refractory CD19+ B cell malignancies including acute lymphocytic leukemia (ALL), non-Hodgkin's lymphoma containing Diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), or small lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia(BPLL), Lymphoplasmacytic Lymphoma, Marginal Zone Lymphoma (MZL).
- Definition of relapse or refractory as below:
Key exclusion criteria (15 listed)
- Current use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary.
- Pregnancy or lactation
- Known allergic reactions to components used in the intervention protocols or medication regimens in this study
- Active Febrile illness
- Treatment with another investigational drug or other intervention within 30 days or 5 half-lives.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD19 Chimeric Antigen Receptor (CAR) T CellsThis study seeks to examine the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B cell surface antigen CD19 following administration of chemotherapy lymphodepletion regimen in children and adults with relapsed/refractory B cell malignancies. The overall goal of this study is to validate the safety profile of administration CD19 CAR T cells and describe the toxicities in children and adults with relapsed/ refractory B cell malignancies. Each patient implements leukapheresis 2 weeks after enrollment and infuse CD19 CAR-T cell around 2 weeks after leukapheresis, and administrated chemotherapy lymphodepletion regimen 1 week before infusion. Furthermore, the treated subject would be following up around 2 years. | Drug | CD19 Chimeric Antigen Receptor (CAR) T Cells |
Primary outcome
80% Proportion of products successfully manufactured meeting the established release criteria with a goal of at least CAR-T cell 1 X 10^6 cells/kilogram.
Time frame: 3 years
To examine the feasibility of manufacture of autologous CD19 CAR T-cells at a minimum target dose of 1 X 106 cells/kilogram using the Miltenyi CliniMACS Prodigy® automated system
Incidence and severity of adverse events
Time frame: 3 years
To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19
Incidence and severity of Dose Limited Toxicities
Time frame: 3 years
Find the recommended phase II dose (RP2D) for recurrent/refractory B cell malignancies
Incidence and severity of Maximum Toxicity Dose
Time frame: 3 year
Find the recommended phase II dose (RP2D) for recurrent/refractory B cell malignancies
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19 Chimeric Antigen Receptor (CAR) T Cells in people with Relapsed/Refractory B-Cell Malignancies, run by National Taiwan University Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jih-Luh Tang (886-0-72651057, tangntuh@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
80% Proportion of products successfully manufactured meeting the established release criteria with a goal of at least CAR-T cell 1 X 10^6 cells/kilogram. (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.